This study will examine aspects of the regulation of fetal lung maturation and the synthesis of fatty acids in fetal lung in culture. Previous studies with fetal rat lung organ cultures have revealed that there are supra-additive interactions between dexamethasone and theophylline or triiodothyronine with regard to the synthesis of disaturated phosphatidylcholine, the major surface active phospholipid. Possible mechanisms for these interactions will be explored at the receptor and translational levels and in vivo studies will be performed to determine if the administration of combinations of hormones is more effective than that of single hormones alone. These agents are now being used clinically in attempts to prevent the Respiratory Distress Syndrome of the newborn so that this study may ultimately have clinical implications. Fetal rat and rabbit lung continue maturation in organ culture in the absence of added serum or hormones. Removal from circulating inhibitors and stimulation by endogenous mesenchymal factors will be examined as possible causes of this phenomenon. Ongoing studies of the role of the mesenchyme in the regulation of fetal rat lung epithelial cell morphogenesis, surface-active phospholipid synthesis, the ontogeny of the corticosteroid and thyroid receptor and as mediators of the response to hormonal stimulation will be continued. Little information is currently available on the pathways of fatty acid synthesis in the non-adult type II cell. "Slices" prepared from the type II cell rich peripheral rim of organotypic cultures of fetal rat lung will be used to study de novo fatty acid synthesis and the fatty acid components of disaturated phosphatidylcholine in the developing type II cell. These studies should provide further information on the regulation and biosynthesis of pulmonary surfactant in the fetus.